1. Field of the Invention
This invention relates to fatty acid derivatives, particularly sixteen carbon atom carboxylic acids which are substituted by a 16-phenoxy or a 16-phenylthio substituent. This invention also relates to the use of these compounds for the treatment of diseases characterized by inflammation, to pharmaceutical compositions containing these derivatives and to processes for preparing these derivatives.
2. Related Disclosures
Arachidonic acid is a naturally occurring polyunsaturated fatty acid, also known as eicosa 5(Z), 8(Z), 11(Z), 14(Z)-tetraenoic acid. It was first isolated from the liver and has been synthesised by several methods, see, for example, A. I. Raschlind et al, J. Org. Chem., 26, 2688, (1961), and J. M. Osbond et al, Chem. and Ind. (London), 1959, 1288. Arachidonic acid is converted to a variety of naturally occuring compounds in the mammalian metabolism, including, for example, prostaglandins, thromboxanes, and leukotrienes. All of the major metabolic products of arachidonic acid are known to be involved in various disease states. Among the enzymes involved in this complex biochemical process, known as the "arachidonic acid cascade", are fatty acid cyclooxygenase and lipoxygenase. A more complete discussion of the arachidonic acid cascade can be found at Chem. and Eng. News, Aug. 16, 1982, 30-44. Certain arachidonic acid derivatives have been prepared. These include eicosa-5,8,11,14-tetraynoic acid, disclosed by J. M. Osbond et al, J. Chem. Soc., 2779 (1961); eicosa-8(Z),11(Z),14(Z)-trien-5-ynoic acid, described by H. Heslinga et al. in Recueil, 94, 262 (1975); nonadeca-5(Z),8(Z),11(Z),14(Z)-trien-5-ynoic acid described by R. K. Beerthuis et al. in Recueil, 87, 461 (1968); and octadeca-5,8,11,14-tetraynoic acid described by R. K. Beerthuis et al. in Recueil, 90, 943 (1971).
A new family of sixteen carbon atom carboxlic acid derivatives related to arachidonic acid have now been discovered. These compounds inhibit lipoxygenase and are useful for treating disease states characterized by inflammation.